The Role of Porphyromonas gingivalis Outer Membrane Vesicles in Periodontal Disease and Related Systemic Diseases

Zhang, Zhiying; Liu, Dongjuan; Liu, Sai; Zhang, Shuwei; Pan, Yaping

doi:10.3389/fcimb.2020.585917

Cited by 135 publications

(143 citation statements)

References 105 publications

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“…Through long-distance transmission, Pg OMVs can reach distant target organs and induce related systemic diseases. A recent review of this subject [142] indicates the correlation between Pg OMVs and systemic system diseases. First, in cardiometabolic diseases, Pg OMVs attenuate insulininduced Akt/GSK-3␤ signaling in hepatic HepG2 cells, thereby causing changes in glucose metabolism in the liver and promoting the development of diabetes.…”

Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis Outer Membrane Vesicles as the Major Driver of and Explanation for Neuropathogenesis, the Cholinergic Hypothesis, Iron Dyshomeostasis, and Salivary Lactoferrin in Alzheimer’s Disease

Nara¹,

Sindelar²,

Penn

et al. 2021

JAD

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Porphyromonas gingivalis (Pg) is a primary oral pathogen in the widespread biofilm-induced “chronic” multi-systems inflammatory disease(s) including Alzheimer’s disease (AD). It is possibly the only second identified unique example of a biological extremophile in the human body. Having a better understanding of the key microbiological and genetic mechanisms of its pathogenesis and disease induction are central to its future diagnosis, treatment, and possible prevention. The published literature around the role of Pg in AD highlights the bacteria’s direct role within the brain to cause disease. The available evidence, although somewhat adopted, does not fully support this as the major process. There are alternative pathogenic/virulence features associated with Pg that have been overlooked and may better explain the pathogenic processes found in the “infection hypothesis” of AD. A better explanation is offered here for the discrepancy in the relatively low amounts of “Pg bacteria” residing in the brain compared to the rather florid amounts and broad distribution of one or more of its major bacterial protein toxins. Related to this, the “Gingipains Hypothesis”, AD-related iron dyshomeostasis, and the early reduced salivary lactoferrin, along with the resurrection of the Cholinergic Hypothesis may now be integrated into one working model. The current paper suggests the highly evolved and developed Type IX secretory cargo system of Pg producing outer membrane vesicles may better explain the observed diseases. Thus it is hoped this paper can provide a unifying model for the sporadic form of AD and guide the direction of research, treatment, and possible prevention.

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Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis Outer Membrane Vesicles as the Major Driver of and Explanation for Neuropathogenesis, the Cholinergic Hypothesis, Iron Dyshomeostasis, and Salivary Lactoferrin in Alzheimer’s Disease

Nara¹,

Sindelar²,

Penn

et al. 2021

JAD

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“…Given that NTHi and M. catarrhalis have been shown to release OMVs, that can activate host immune responses as well as potentially support bacterial colonization, they may provide a novel mechanism contributing to the nature of chronic and recurrent bacterial infections in AECOPD and systemic disease. In support of this, a recent review highlighted the role of Porphyromonas gingivalis in promoting the development of related systemic diseases including diabetes and cardiovascular disease through long distance transmission of OMVs (140,141). Further research is, therefore, required to determine role of OMVs in COPD and other systemic diseases.…”

Section: Immune and Inflammatory Role Of Evs In Response To Respiratory Infectionmentioning

confidence: 98%

The Role of Extracellular Vesicles as a Shared Disease Mechanism Contributing to Multimorbidity in Patients With COPD

et al. 2021

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Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Individuals with COPD typically experience a progressive, debilitating decline in lung function as well as systemic manifestations of the disease. Multimorbidity, is common in COPD patients and increases the risk of hospitalisation and mortality. Central to the genesis of multimorbidity in COPD patients is a self-perpetuating, abnormal immune and inflammatory response driven by factors including ageing, pollutant inhalation (including smoking) and infection. As many patients with COPD have multiple concurrent chronic conditions, which require an integrative management approach, there is a need to greater understand the shared disease mechanisms contributing to multimorbidity. The intercellular transfer of extracellular vesicles (EVs) has recently been proposed as an important method of local and distal cell-to-cell communication mediating both homeostatic and pathological conditions. EVs have been identified in many biological fluids and provide a stable capsule for the transfer of cargo including proteins, lipids and nucleic acids. Of these cargo, microRNAs (miRNAs), which are short 17-24 nucleotide non-coding RNA molecules, have been amongst the most extensively studied. There is evidence to support that miRNA are selectively packaged into EVs and can regulate recipient cell gene expression including major pathways involved in inflammation, apoptosis and fibrosis. Furthermore changes in EV cargo including miRNA have been reported in many chronic diseases and in response to risk factors including respiratory infections, noxious stimuli and ageing. In this review, we discuss the potential of EVs and EV-associated miRNA to modulate shared pathological processes in chronic diseases. Further delineating these may lead to the identification of novel biomarkers and therapeutic targets for patients with COPD and multimorbidities.

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“…These findings suggest that bacteremia may not be a temporary nor a localized problem. Furthermore, it has been revealed that microbes can be found in the lungs of healthy people [5,85,86] and cancer patients [87], the placenta of healthy pregnant women, albeit controversial [1-4], and the brains in Alzheimer's disease (AD) [88][89][90][91], which had long been considered sterile.…”

Section: Focal Infection Theory and Leaky Gummentioning

confidence: 99%

Leaky Gum: The Revisited Origin of Systemic Diseases

Park¹,

Park²,

Lee³

et al. 2022

Preprint

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The oral cavity is the gateway for microorganisms into your body where they disseminate not only to the directly connected respiratory and digestive tracts, but also to the many remote organs. Oral microbiota, traveling to the end of the intestine and circulating our body through blood vessels, not only affect a gut microbiome profile, but also many systemic diseases. By gathering information accumulated from the era of focal infection theory to the age of revolution in microbiome research, we propose a pivotal role of “leaky gum”, as an analogy of “leaky gut”, to underscore the importance of the oral cavity in systemic health. The oral cavity has unique structures, the gingival sulcus (GS) and the junctional epithelium (JE) below the GS, which are rarely found anywhere else in our body. The JE is attached to the tooth enamel and cementum by hemidesmosome (HD), which is structurally weaker than desmosome and is thus vulnerable to microbial infiltration. In the GS, microbial biofilms can build up for life, unlike the biofilms on the skin and intestinal mucosa that fall off by natural process. Thus, we emphasize that the GS and the JE are the weakest leaky point for microbes to invade human body, making the leaky gum just as important as, or even more important than, the leaky gut.

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The Role of Porphyromonas gingivalis Outer Membrane Vesicles in Periodontal Disease and Related Systemic Diseases

Cited by 135 publications

References 105 publications

Porphyromonas gingivalis Outer Membrane Vesicles as the Major Driver of and Explanation for Neuropathogenesis, the Cholinergic Hypothesis, Iron Dyshomeostasis, and Salivary Lactoferrin in Alzheimer’s Disease

Porphyromonas gingivalis Outer Membrane Vesicles as the Major Driver of and Explanation for Neuropathogenesis, the Cholinergic Hypothesis, Iron Dyshomeostasis, and Salivary Lactoferrin in Alzheimer’s Disease

The Role of Extracellular Vesicles as a Shared Disease Mechanism Contributing to Multimorbidity in Patients With COPD

Leaky Gum: The Revisited Origin of Systemic Diseases

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